AB0394 CLINICAL OUTCOMES UP TO WEEK 48 OF ONGOING FILGOTINIB (FIL) RHEUMATOID ARTHRITIS (RA) LONG-TERM EXTENSION (LTE) TRIAL OF BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUG (bDMARD) INADEQUATE RESPONDERS (IR) INITIALLY ON FIL OR PLACEBO IN A PHASE 3 PARENT STUDY (PS)
Authors: M. H. Buch, T. Takeuchi, V. Rajendran, J. E. Gottenberg, A. Pechonkina, Y. Tan, Q. Gong, K. Van Beneden, R. Caporali
Journal: Annals of the Rheumatic Diseases (2022)

Background The preferential Janus kinase-1 inhibitor FIL is approved for treatment of moderate to severe active RA in Europe and Japan. Objectives Efficacy and safety of FIL were assessed in patients (pts) with IR to bDMARDs in a LTE trial ( NCT03025308 ) enrolled from a Phase 3 PS ( NCT02873936 ). 1 Methods bDMARD-IR pts received FIL 200 mg (FIL200), FIL 100 mg (FIL100), or placebo (PBO), all with stable conventional synthetic (cs)DMARDs up to 24 weeks (W). At W14 of the PS, pts with IR to FIL or PBO (&lt;20% improvement in swollen [66] and tender [68] joint counts) switched to standard of care (SOC; investigator’s choice of treatment). Pts completing the PS on FIL, PBO, or SOC could enter the LTE. PS FIL pts were maintained, blinded, on their FIL dose; PS PBO and PS SOC pts were rerandomized, blinded, to FIL200 or FIL100. Efficacy data to LTE W48 and safety data to data cutoff (June 1, 2020) are reported. Results The PS included 147, 153, and 148 pts on FIL200, FIL100, and PBO. Pts continuing on LTE FIL200 and FIL100 at data cutoff: 80/121 (66%) and 76/110 (69%) from PS FIL200 and FIL100; 35/47 (75%) and 32/46 (70%) from PS PBO, and 13/23 (57%) and 13/22 (59%) from PS SOC. LTE baseline (BL) characteristics were similar in FIL200 and FIL100 pts. During LTE, PS FIL ACR20/50/70 response rates decreased modestly by W48 (Figure 1). Among PS PBO pts, response rates were lower at LTE BL, reaching similar levels to PS FIL pts by W48; rates increased to W48 in PS SOC pts on either FIL dose but not to levels of other groups. Percentages of pts attaining DAS28(CRP) ≤3.2, DAS28(CRP) &lt;2.6, CDAI ≤10, and CDAI ≤2.8 were maintained up to W48 for FIL/FIL pts. PBO/FIL and SOC/FIL pts showed similar patterns to ACR responses (Figure 1). Exposure-adjusted incidence rates (EAIRs)/100 pt-years of exposure for treatment-emergent adverse events (TEAE), serious AEs, and serious infection were higher in SOC/FIL pts vs FIL/FIL or PBO/FIL pts, but samples were small and confidence intervals overlapped. There were 5 deaths (Table 1). Table 1. EAIRs of TEAEs in LTE, as of June 1, 2020 EAIR (95% CI) FIL200+csD → FIL200+csD n=121PYE 228.4 PBO+csD → FIL200+csD n=47PYE 98.1 SOC+csD → FIL200+csD n=23PYE 42.1 FIL100+csD → FIL100+csD n=110PYE 223.3 PBO+csD → FIL100+csD n=46PYE 91.1 SOC+csD → FIL100+csD n=22PYE 38.2 TEAE 46.9 (38.8, 56.6) 38.7 (28.2, 53.2) 52.2 (34.4, 79.3) 40.3 (32.8, 49.5) 40.6 (29.4, 56.1) 49.8 (31.8, 78.0) TEAE Grade ≥3 10.5 (7.0, 15.7) 10.2 (5.5, 18.9) 19.0 (9.5, 38.0) 10.3 (6.8, 15.5) 13.2 (7.5, 23.2) 18.3 (8.7, 38.5) TE serious AE 12.3 (8.5, 17.8) 12.2 (6.9, 21.5) 21.4 (11.1, 41.1) 8.1 (5.1, 12.8) 13.2 (7.5, 23.2) 21.0 (10.5, 41.9) Death 1.3 (0.4, 4.1) 1.0 (0, 5.7) 0 (0, 8.8) 0.4 (0.1, 3.2) 0 (0, 4.0) 0 (0, 9.7) TE infections 34.2 (27.4, 42.6) 22.4 (14.8, 34.1) 35.6 (21.5, 59.1) 22.4 (17.0, 29.5) 26.3 (17.7, 39.3) 39.3 (23.7, 65.2) TE serious infections 3.5 (1.8, 7.0) 2.0 (0.5, 8.2) 7.1 (2.3, 22.1) 0.9 (0.2, 3.6) 2.2 (0.5, 8.8) 7.9 (2.5, 24.4) Opportunistic infections 0 (0, 1.6) 0 (0, 3.8) 0 (0, 8.8) 0 (0, 1.7) 0 (0, 4.0) 0 (0, 9.7) TE herpes zoster 2.2 (0.7, 5.1) 1.0 (0.1, 7.2) 0 (0, 8.8) 0 (0, 1.7) 2.2 (0.5, 8.8) 2.6 (0.1, 14.6) TE MACE (adjudicated) 1.3 (0.4, 4.1) 1.0 (0.1, 7.2) 0 (0, 8.8) 0.9 (0.2, 3.6) 1.1 (0.2, 7.8) 0 (0, 9.7) TE DVT/PE (adjudicated) 0.9 (0.2, 3.5) 0 (0, 3.8) 2.4 (0.1, 13.2) 0.4 (0.1, 3.2) 0 (0, 4.0) 0 (0, 9.7) Malignancies (excluding NMSC) 1.3 (0.4, 4.1) 3.1 (1.0, 9.5) 4.7 (0.6, 17.2) 1.8 (0.7, 4.8) 3.3 (1.1, 10.2) 0 (0, 9.7) NMSC 0 (0, 1.6) 0 (0, 3.8) 4.7 (0.6, 17.2) 0 (0, 1.7) 0 (0, 4.0) 0 (0, 9.7) DVT, deep vein thrombosis; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PE, pulmonary embolism; TE, treatment-emergent Conclusion Efficacy was mostly maintained in PS FIL pts up to W48. Response among PS PBO and SOC pts increased from BL to W48, but response in PS SOC pts continued to be lower than in other groups; these pts may represent a refractory population. FIL safety was largely consistent between PS and LTE. References [1]Genovese MC et al. JAMA 2019;322:315–25. Acknowledgements This study was funded by Gilead Sciences, Inc., Foster City, CA. Medical writing support was provided by Claudine Bitel, PhD, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA. Disclosure of Interests Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer, Tsutomu Takeuchi Speakers bureau: AbbVie, AYUMI, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly Japan, Gilead Sciences, Mitsubishi-Tanabe, Novartis, Pfizer Japan, and Sanofi, Consultant of: Astellas, Chugai, and Eli Lilly Japan, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan, Vijay Rajendran Shareholder of: Galapagos, Employee of: Galapagos, Jacques-Eric Gottenberg Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., Roche, Sanofi Genzyme, and UCB, Consultant of: Bristol Myers Squibb, Sanofi Genzyme, and UCB, Grant/research support from: Bristol Myers Squibb and Pfizer, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Qi Gong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, Fresenius-Kabi, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB